Vapor Trail: Electronic Noses Sniff Bad Breath for Signs of Disease

If the ancient Greek physician Hippocrates diagnosed you with fetor hepaticus (bad liver breath), it would not be an insult but a friendly warning. It meant the scent of your breath indicated you were going into liver failure. Much of ancient Greek medical knowledge has fallen into obscurity, but using the breath as an indicator of health remains. Researchers have for years worked to develop accurate, inexpensive and portable electronic olfactory sensing technology that can be used to detect and monitor asthma, kidney disease, high cholesterol and a number of other conditions.

A variety of approaches are being used to develop what are referred to, inevitably, as e-noses—devices that use an array of chemical sensors for reading odors and a mechanism for identifying different scents. They typically cost about $8,000 to $30,000. Most rely on bulky gas chromatography and mass spectroscopy systems to identify airborne compounds. They generally require several breaths saved in a balloon. Other breath-analyzing devices, such as alcohol Breathalyzers, use technologies that are not sufficiently accurate for medical use.

An e-nose's ability to recognize a particular odor and flag it as a warning sign has been hindered by lack of specificity—that is, the inability to detect and quantify a single substance in an exhalation that contains hundreds of compounds. Several new approaches aim to overcome that problem. One promising project involves a team of Stony Brook University, The State University of New York, researchers led by associate professor of materials science and engineering Perena Gouma, who have developed an e-nose that uses semiconducting ceramic sensors to detect disease and measure metabolic functions.

According to Gouma, the sensor is highly sensitive to gaseous disease-signalling markers in the breath—it can detect specific molecules in parts per billion. The sensor chip is covered with spaghettilike metal oxide fibers that have diameters ranging from one to 100 nanometers (a nanometer is one billionth of a meter). The nanofibers' crystalline structure and the atomic configuration on their surfaces determine which compound can be detected. For instance, gases such as carbon monoxide and methane stick to a nanofiber oxide sensor whose atoms have a tetragonal (four-sided) arrangement. Nanofibers can be made in large quantities and tweaked during production to respond to different compounds. Once the e-nose detects its target molecule, its concentration is shown on a digital display.

Breath contains hundreds of volatile organic compounds that are by-products of our metabolism. Certain diseases alter the mix of gases, introducing new compounds or altering the levels of existing ones, Gouma says. One sensor could detect acetone in the breath of diabetics to determine whether they need to increase their insulin doses. Another could measure nitric oxide in asthmatics' breath to detect an impending or worsening asthma attack.

Gouma's group is also developing e-noses to detect the organic compound isoprene to measure cholesterol levels, ammonia to detect kidney disease, and a mix of ammonia and ketones to get a whiff of liver disease. The researchers are also developing an e-nose that can distinguish between two similar chemical structures—alkanes and alkenes—for early detection of lung cancer, Gouma says.

These prototype e-noses resemble hardcover novels with a mouthpiece attached at one end. Gouma anticipates the final design will be about the size of a key ring. She expects at least one of her e-noses will be ready for clinical testing within a year. Unlike other e-noses, Gouma's require only a single breath to detect specific compounds, she says. This means for some conditions breath tests can be performed in lieu of blood samples. Gouma anticipates such handheld e-noses such as these could cost as little as $20 each.

Nathan Lewis, a chemistry professor at the California Institute of Technology, is also developing e-nose technology. His system relies on polymer films rather than nanoscale wires to identify compounds. But he says with respect to Gouma's gizmos: "Ceramic nanosensing technology is one promising approach for medical and other electronic-nose applications. [Gouma's] work is a significant step forward in that regard."

Other researchers, however, are skeptical about an e-nose's ability to analyze individual components of even simple mixtures of volatile organic compounds (VOC). "Among the challenges to obtaining clinically useful measurements of breath VOCs, such as acetone or other possible disease markers, one of the toughest is reliably differentiating the marker or markers from the background VOCs found in breath," says Edward Zellers, an environmental health sciences professor at the University of Michigan. He adds, "This has not yet been demonstrated with any e-nose technology of which I am aware." Still, although he is wary of e-noses being used for disease diagnosis, Zellers says Gouma's technology has promise as a means of detecting individual reactive inorganic markers such as nitric oxide and ammonia.

As Hippocrates may have attested, promising medical ideas frequently do not come to pass. Patients should not hold their breath in anticipation of inexpensive handheld e-noses until the technology proves it is up to snuff in clinical trials.